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Systemic Lupus Erythematosus, with focus on vascular wall changes, cardiac risk-factor awareness and cardiovascular events

Bengtsson, Christine LU (2010) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2010:131.
Abstract (Swedish)
Popular Abstract in Swedish

SAMMANFATTNING PÅ SVENSKA



Systemisk Lupus Erytematosus (SLE) är en kronisk inflammatorisk system sjukdom. Sjukdomen yttrar sig med stor variation, både avseende vilka organ områden och med vilken intensitet olika organ kan bli engagerade. Genom åren har prognosen för sjukdomen i sig dramatiskt förbättrats, genom att alla typer av organ manifestationer kan behandlas. Senaste decennierna har emellertid forskningen visat att även hjärt- och kärlsjukdom kan påverkasjukligheten och dödligheten vid SLE. Studier har genomförts bl a för att kartlägga risk för hjärt- kärl sjukdom, tidiga manifestationer av åderförkalkning samt olika risk faktorer för hjärt-kärl sjukdom vid SLE.... (More)
Popular Abstract in Swedish

SAMMANFATTNING PÅ SVENSKA



Systemisk Lupus Erytematosus (SLE) är en kronisk inflammatorisk system sjukdom. Sjukdomen yttrar sig med stor variation, både avseende vilka organ områden och med vilken intensitet olika organ kan bli engagerade. Genom åren har prognosen för sjukdomen i sig dramatiskt förbättrats, genom att alla typer av organ manifestationer kan behandlas. Senaste decennierna har emellertid forskningen visat att även hjärt- och kärlsjukdom kan påverkasjukligheten och dödligheten vid SLE. Studier har genomförts bl a för att kartlägga risk för hjärt- kärl sjukdom, tidiga manifestationer av åderförkalkning samt olika risk faktorer för hjärt-kärl sjukdom vid SLE. Emellertid är dessa områden inte till fullo klarlagda.

Syftet med denna avhandling var att ytterliga belysa hjärt-kärlsjukdom vid SLE. Detta gjordes genom att studera förändringar i blodkärlsväggarna och reaktivitet i de små blodkärlen hos SLE patienter i förhållande till kontroller. Dessutom genom att undersöka patienternas kännedom om riskfaktorer för utveckling av hjärt-kärlsjukdom, följsamhet till råd om förbättring samt dokumentation av dessa riskfaktorer. Vidare att kartlägga förekomst av hjärt-kärlsjukdom vid SLE i förhållande till befolkningen i samma geografiska område och att identifiera faktorer, som kan förutsäga risk (prediktorer) för hjärt-kärl sjukdom.

I studie I undersöktes, som ett mått på kärlsjukdom, artärernas styvhet med ultraljud (“echo-tracking”) där en matematisk datoriserad funktion beräknar styvheten av artärerna. I studie II beräknas styvheten av artärerna genom kalkylering av pulsvågens hastighet genom kärlträdet.I studie I och II visades att det förelåg en ökad styvhet av artärväggar hos SLE patienterna. Detta var vid undersökningen i studie II associerat med inflammationsmarkörer och i studie I noterades en tendens till mindre kärlstyvhet hos patienter med antimalaria medicinering.

Reaktiviteten i små blodkärl i huden är ett annat tänkbart mått på kärlsjukdom och undersöktes med ultraljud-Doppler teknik efter stimulering med två olika substanser (studie III). På detta sätt kan man avgöra vilken del av blodkärlet som på verkar svaret på stimuleringen. Vid denna undersökning visades att malariamedicin, kortison och blodförtunnande behandling, vid SLE påverkade reaktiviteten i blodkärlet, emellertid sågs ingen skillnad mellan SLE patienter och kontroll personer.

Studie IV var en enkät undersökning där patienternas kännedom om riskfaktorernas betydelse för utveckling av hjärt-kärlsjukdom efterfrågades. Likaså ingick frågor om förekomst av dessa riskfaktorer, huruvida patienterna hade fått information om förbättringsåtgärder av dessa och om dessa råd hade följts. Överenstämmelsen angående riskfaktorernas förekomst jämfördes mellan enkät svar och journal dokumentation. Rökning, hyperkolesterolemi och övervikt ansågs av mer än 70% av patienterna såsom “mycket viktiga” , medan färre än 50% graderade diabetes “mycket viktigt” för utveckling av hjärt-kärl sjukdom. Överenstämmelsen mellan journal och enkät avseende förekomst av risk faktorer var låg gällande de livsstils relaterade faktorerna. Patienternas följsamhet till rekommendationer om förbättring av riskfaktorer varierade. Högst följsamhet angavs för medicinering överlag, medan råd om livsstilsförändring följdes i lägre grad.

Insjuknande i hjärt-kärlsjukdom vid SLE under en sju års tid undersöktes i studie V. Det visades att risken för hjärtinfarkt var dubblerad hos SLE patienter överlag och jämfört med populationen i samma region, medan det bland kvinnor i åldern 40-49 år noterades en nio gånger ökad risk för hjärtinfakt. Hos samma grupp av kvinnor var risken för hjärtinfarkt och stroke åtta gånger förhöjd. SLE patienterna löpte risk att drabbas tidigare av hjärtinfarkt eller stroke jämfört med matchade kontroller och detta kunde predikteras av högt blodtryck. Inom SLE gruppen predikterades insjuknande i hjärtinfarkt eller stroke av sjukdomsaktivitet och förekomst av vissa antikroppar.

Sammanfattningsvis noterades tecken till förändringar i kärlväggarna och i reaktiviteten i de minsta kärlen hos SLE patienterna. Viss medicinering förefall ha inverkan på dessa resultat. Dessa fynd borde bli föremål för uppföljande studier av den ökade kärlstyvheten och vilka kärlväggsmekanismer som påverkas av olika mediciner. Vidare framkom att det föreligger en påtagligt ökad risk för hjärt-kärl sjukdom bland SLE patienter, med tyngdpunkten hos medelålders kvinnor. Vilket ytterligare understryker att det finns behov av förbättrad patientinformation och nya strategier för förändring av framför allt livsstilsrelaterade riskfaktorer för hjärt-kärl sjukdom. (Less)
Abstract
Systemic Lupus Erythematosus is an autoimmune disease with a wide range of disease manifestations with respect to severity and magnitude of organ involvement. An increased risk of cardiovascular disease (CVD) compared with the general population causes both morbidity and mortality in SLE patients. Consequently prevention, early detection and treatment of arteriosclerotic manifestations are of high priority for the clinician.

The aims in the present thesis focused on identifying non-invasive possible markers associated with atherosclerosis in SLE patients and in comparison with controls. Cardiac risk factor (CRF) awareness among patients, the documentation of these factors in patients records and the adherence to given advice... (More)
Systemic Lupus Erythematosus is an autoimmune disease with a wide range of disease manifestations with respect to severity and magnitude of organ involvement. An increased risk of cardiovascular disease (CVD) compared with the general population causes both morbidity and mortality in SLE patients. Consequently prevention, early detection and treatment of arteriosclerotic manifestations are of high priority for the clinician.

The aims in the present thesis focused on identifying non-invasive possible markers associated with atherosclerosis in SLE patients and in comparison with controls. Cardiac risk factor (CRF) awareness among patients, the documentation of these factors in patients records and the adherence to given advice about changing risk factor behaviour was evaluated. Furthermore, the incidence of CVD among SLE patients compared with the general population and matched controls was analysed and predictors of cerebrovascular events evaluated.

Arterial stiffness was measured using two methods: firstly, using an ultrasound echo-tracking system it was found that SLE patients without CVD had an increased stiffness of the popliteal artery (p=0.005), and that the diameter of the common carotid artery was increased in SLE patients compared with controls (Paper I). Secondly, the aortic pulse wave velocity (PWV), measured by arterial tonometry, was found to be increased reflecting stiffness (p<0.01). An association between C-reactive protein, and complement component 3 and the increase in PWV was also noted (Paper II).

Cutaneous microvascular reactivity was measured using an iontophoretic laser-doppler technique after acetylcholine or nitroprusside stimulation with no difference between SLE patients and controls being found (Paper III). However, patients prescribed anti-malarial treatment had an elevated endothelium independent reactivity (p<0.005). Whilst higher doses of prednisone (≥5mg/day) were associated with a decrease in the endothelial dependent reactivity (p<0.05) warfarin treatment increased the endothelial dependent reactivity (p<0.05).

A validated questionnaire was used to study CRFs (Paper IV). More than 70% of the patients identified obesity, smoking and hypercholesterolaemia as being very important CRFs. The agreement between medical record documentation and the patients´ own report for hypertension, being overweight and hypercholesterolaemia was moderate (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). There was a notable difference in the self-reported compliance to advice, with good adherence to prescribed medications but poor adherence to lifestyle changes.

An overall elevated risk for myocardial infarction (MI) in SLE patients compared with the general population was demonstrated, i.e.., 2.31 (95%CI 1.34-3.7) which was further raised among middle aged female patients to 8.7 (95%CI 1.1-31.4) (Paper V). In this patient group, the SIR for an MI and/or stroke was 8.00 (95%CI 1.65-23.38). The time to a cardiovascular event (CVE) was significantly shorter among SLE patients compared with matched controls (p<0.001) and predicted by hypertension. An event in a SLE patient was predicted by a high SLEDAI score and the presence of anti-cardiolipin-IgG antibodies (aCL-IgG) when adjusted for age and a previous MI.

In conclusion, the arterial vessel walls are stiffer and show signs of early ageing in SLE patients. An association with elevated C-reactive protein levels was also noted. Both endothelium dependent and independent cutaneous microvascular reactivity is influenced by medication. Patients’ knowledge of, and adherence to advice regarding modification of CRFs are in need of improvement. The risk for a CVE, and an MI per se, in female SLE patients is notably elevated and the overall risk for an MI is doubled. The time to a CVE in SLE patients is shorter and predicted by hypertension. In SLE patients an event is also predicted by greater disease activity and presence of aCL-IgG antibodies. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Förre, Öystein, Dept of Rheumatology, Rikshospitalet University Hospital, Oslo, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
microvascular reactivity, arteria stiffness, cardiac risk factors, Cardiovascular event, SLE
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2010:131
pages
104 pages
publisher
Section of Rheumatology
defense location
Segerfalksalen, BMC
defense date
2010-12-17 13:00
ISSN
1652-8220
ISBN
978-91-86671-47-1
language
English
LU publication?
yes
id
b2c8b9ff-a080-4cf6-9112-9280669ed662 (old id 1729739)
date added to LUP
2010-11-29 13:05:22
date last changed
2018-05-29 09:48:41
@phdthesis{b2c8b9ff-a080-4cf6-9112-9280669ed662,
  abstract     = {Systemic Lupus Erythematosus is an autoimmune disease with a wide range of disease manifestations with respect to severity and magnitude of organ involvement. An increased risk of cardiovascular disease (CVD) compared with the general population causes both morbidity and mortality in SLE patients. Consequently prevention, early detection and treatment of arteriosclerotic manifestations are of high priority for the clinician. <br/><br>
The aims in the present thesis focused on identifying non-invasive possible markers associated with atherosclerosis in SLE patients and in comparison with controls. Cardiac risk factor (CRF) awareness among patients, the documentation of these factors in patients records and the adherence to given advice about changing risk factor behaviour was evaluated. Furthermore, the incidence of CVD among SLE patients compared with the general population and matched controls was analysed and predictors of cerebrovascular events evaluated.<br/><br>
Arterial stiffness was measured using two methods: firstly, using an ultrasound echo-tracking system it was found that SLE patients without CVD had an increased stiffness of the popliteal artery (p=0.005), and that the diameter of the common carotid artery was increased in SLE patients compared with controls (Paper I). Secondly, the aortic pulse wave velocity (PWV), measured by arterial tonometry, was found to be increased reflecting stiffness (p&lt;0.01). An association between C-reactive protein, and complement component 3 and the increase in PWV was also noted (Paper II).<br/><br>
Cutaneous microvascular reactivity was measured using an iontophoretic laser-doppler technique after acetylcholine or nitroprusside stimulation with no difference between SLE patients and controls being found (Paper III). However, patients prescribed anti-malarial treatment had an elevated endothelium independent reactivity (p&lt;0.005). Whilst higher doses of prednisone (≥5mg/day) were associated with a decrease in the endothelial dependent reactivity (p&lt;0.05) warfarin treatment increased the endothelial dependent reactivity (p&lt;0.05).<br/><br>
A validated questionnaire was used to study CRFs (Paper IV). More than 70% of the patients identified obesity, smoking and hypercholesterolaemia as being very important CRFs. The agreement between medical record documentation and the patients´ own report for hypertension, being overweight and hypercholesterolaemia was moderate (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). There was a notable difference in the self-reported compliance to advice, with good adherence to prescribed medications but poor adherence to lifestyle changes.<br/><br>
An overall elevated risk for myocardial infarction (MI) in SLE patients compared with the general population was demonstrated, i.e.., 2.31 (95%CI 1.34-3.7) which was further raised among middle aged female patients to 8.7 (95%CI 1.1-31.4) (Paper V). In this patient group, the SIR for an MI and/or stroke was 8.00 (95%CI 1.65-23.38). The time to a cardiovascular event (CVE) was significantly shorter among SLE patients compared with matched controls (p&lt;0.001) and predicted by hypertension. An event in a SLE patient was predicted by a high SLEDAI score and the presence of anti-cardiolipin-IgG antibodies (aCL-IgG) when adjusted for age and a previous MI.<br/><br>
In conclusion, the arterial vessel walls are stiffer and show signs of early ageing in SLE patients. An association with elevated C-reactive protein levels was also noted. Both endothelium dependent and independent cutaneous microvascular reactivity is influenced by medication. Patients’ knowledge of, and adherence to advice regarding modification of CRFs are in need of improvement. The risk for a CVE, and an MI per se, in female SLE patients is notably elevated and the overall risk for an MI is doubled. The time to a CVE in SLE patients is shorter and predicted by hypertension. In SLE patients an event is also predicted by greater disease activity and presence of aCL-IgG antibodies.},
  author       = {Bengtsson, Christine},
  isbn         = {978-91-86671-47-1},
  issn         = {1652-8220},
  keyword      = {microvascular reactivity,arteria stiffness,cardiac risk factors,Cardiovascular event,SLE},
  language     = {eng},
  pages        = {104},
  publisher    = {Section of Rheumatology},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Systemic Lupus Erythematosus, with focus on vascular wall changes, cardiac risk-factor awareness and cardiovascular events},
  volume       = {2010:131},
  year         = {2010},
}